During the development of the nervous system, diverse cell types are generated from a pool of pluripotent precursor cells. A critical step in this process is the timely exit of the neural precursors from the mitotic cell cycles, which ensures that correct number and type of neurons are generated. The present research proposal is focused on the question as to, how molecular genetic mechanisms regulate the precise coordination of mitotic cell cycles during nervous system development? We will test the hypothesis that the genes that regulate cell cycle exit are key during neural pattern formation. Previous work from our laboratory has shown has shown that, 1) the rap (retina aberrant in pattern) gene encodes the Fizzy-related (Fzr) protein, an important regulator cell cycle exit. 2) The Rap (Fzr) proteincontainsWD (Trp-Asp) or b- transducin repeat motifs, a conserved protein domain that is found in several important cell cycle regulatory proteins. 3) Loss-of-function mutationsin rap induce abnormal additional mitotic cycles and lead to defective patterning of the developing Drosophila eye. 4) Targeted over-expression of Rap/Fzr in the eye primordial cells causes precocious cell cycle exit, and smaller primordial eye fields, which either eliminate the eye or drastically reduce the size of the adult eye. 5) Although mitosisis inhibited, abnormally large cells that form tumor like structures result from continued endoreplication, cell growth and retinal differentiation. 6) Interestingly, premature over-expression of Rap/Fzr in the eye primordia also induces ectopicantennae. Our results show that rap function is critical for cell cycle exit and a hallmark during pattern formation and morphogenesis in the developing eye. In the present research proposal we will: 1) determine the cellular expression patterns of Rap/Fzr in the developing eye, 2) determine the molecular basis of the rap mutations by DNA sequence and Rap protein analysis. 3) We will use genetic screens to identify and characterize other genes that interact with Rap (Fzr). The results from these experiments will provide insights into the nature of the cellular functions of Rap/Fzr and will be important in understanding mechanisms that regulate cell cycle, neural patterning and growth control.